Personalized Auricular Vagus Nerve Stimulation in Intractable Chronic Low Back Pain (AuriMod)

Personalized Auricular Vagus Nerve Stimulation in Patients With Intractable Chronic Low Back Pain: A Randomized Controlled Pilot Study

One in five people in the general adult population suffer from chronic pain, a figure that is higher than heart disease, cancer, and diabetes combined. A majority of these patients is suffering from chronic back pain. Conventional treatment options offer only a partial response, with many people continuing to suffer severe chronic pain, despite receiving several treatments.

Non-pharmacological treatments by neuromodulation represent a promising treatment modality for these patients. For instance, spinal cord stimulation blocks pain signals travelling to the brain, but requires implantation near the spine with significant clinical risks. Vagus nerve stimulation (VNS) is another neuromodulation modality proposed to alleviate chronic pain. Conventional VNS devices are implanted under the skin on the chest and the electrodes are wired to the left vagus nerve in the neck. However, aside from implantation risks, VNS is often associated with side effects such as swallowing difficulties, due to unwanted stimulation of motoric vagus nerve branches in the neck.

Percutaneous auricular VNS (pVNS) is an emerging technology for stimulation of the auricular branch of the vagus nerve in the pinna of the ear. Specific electrical impulses are applied via three miniature needle electrodes located in the auricle near sensory vagus nerve fibers. Scientific data show that pVNS modulates brain circuits involved in autonomic control and pain processing. pVNS has shown positive effects in chronic low-back pain patients, in a sustainable way with a low side-effect profile. However, the optimal settings of stimulation with regards to personalization remain to be elucidated.

The present prospective, open, randomized, controlled pilot study aims at evaluating the performance of pVNS treatment, using a small wearable stimulation device (AuriMod CT01), comparing personalized and non-personalized stimulation paradigms in patients with chronic low-back pain. Patients will be randomized in one of the following treatment groups (1) Group A: Stimulation with personalized stimulation parameters and amplitude, (2) Group B: Stimulation with personalized stimulation amplitude, (3) Group C: Stimulation without personalization (comparator group).

Patients will be treated for 8 weeks. Patients will receive standardized pain medication including rescue medication in parallel. An additional follow-up period of 12 weeks allows to evaluate sustainable and late-time effects of treatment. Patients will use a therapy management system to monitor outcome.

Study Overview

• Status: Recruiting
• Conditions: Chronic Low-back Pain
• Intervention / Treatment: Device: AuriMod CT01_A; Device: AuriMod CT01_B; Device: AuriMod CT01_C

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Stefan Kampusch, MSc; Phone Number: +436503699271; Email: s.kampusch@aurimod.com

Study Locations

• Austria
  • Carinthia
    • Klagenfurt, Carinthia, Austria, 9020
      • Recruiting
      • Klinikum Klagenfurt am Worthersee
      • Contact: Rudolf Likar, Univ.Prof. Dr.
• Switzerland
  • Geneva, Switzerland, 1217
    • Recruiting
    • Hôpital de la Tour
    • Contact: Christophe Perruchoud, PD Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female aged 18 to 65 years at screening
• Patient has an understanding of the study and its procedures, agrees to its provisions, and gives written informed consent prior to any study-related procedures
• Chronic back pain with or without leg pain (CBLP) persisting for at least 3 months
• A minimum of 70 (out of 180) points on the Computer User Self-Efficacy Scale at the screening visit
• Patient is constant with respect to pain treatment during the screening phase
• A daily average VAS >= 4 on at least half of the days in the screening phase
• Compliance with the daily status reporting requirements as demonstrated by having valid required data entries for all days. It is acceptable if data of one day is missing in the screening phase

Exclusion Criteria:

• Patients with age under 18
• Hemophilia
• Infection, eczema, or psoriasis at application site
• Numbed and desensitized skin at the application site
• Florid malignant diseases
• Mental and physical impairments that represent a source of risk for handling the device
• The presence of a cardiac pacemaker, defibrillator, cochlear implant, or other active implantable device
• Vagal hypersensitivity
• Indication for back surgery
• High-grade spinal stenosis
• Patients with other active implants
• Patients with autonomic disorders
• Patients with diabetes type I or II
• Patients taking Beta-Blockers
• Patients taking drugs carrying the potential risk of arrhythmia (tricyclic medications, Alzheimer drugs, etc.)
• Clinically significant hip or knee arthritis
• Allergy against rescue medication used during the study
• History of Vagus Nerve Stimulation
• Pregnant or nursing female patients
• Patients with arrhythmia, bradycardia, other rhythm disorders or any other clinically significant cardiac anomalies detected during ECG at screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Personalized stimulation parameters and amplitude	Device: AuriMod CT01_A; AuriMod CT01 is a wearable medical device for personalised pain treatment through auricular vagus nerve stimulation. AuriMod CT01 is a battery-operated electrical stimulation device, to be placed behind the ear on the neck. AuriMod CT01 connects to three needle electrodes, which are placed in vagally innervated regions of the auricle. It emits electrical signals with a personalized set of stimulation parameters and adjustable amplitude.
Experimental: Group B; Personalized stimulation amplitude	Device: AuriMod CT01_B; AuriMod CT01 with a fixed set of stimulation parameters and adjustable stimulation amplitude.
Active Comparator: Group C; Non-personalized stimulation	Device: AuriMod CT01_C; AuriMod CT01 with a fixed set of stimulation parameters and amplitude.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average VAS	Change from baseline to End of Treatment (EoT) in average Visual Analogue Scale (VAS; scale 0-10, steps 0.1, 0...no pain, 10...worst pain) during the last 24 hours before the visit	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Max/Min VAS	Change from baseline to EoT in max/min VAS (scale 0-10, steps 0.1, 0...no pain, 10...worst pain)	8 weeks
Average/Max/Min VAS (follow-up; scale 0-10, steps 0.1, 0...no pain, 10...worst pain)	Change from baseline to End of Follow-Up in average/max/min VAS	20 weeks
Normalized average/max/min VAS (scale 0-10, steps 0.1, 0...no pain, 10...worst pain)	Baseline-adjusted area under the max/min/average VAS from baseline to EoT	8 weeks
VAS (follow-up; scale 0-10, steps 0.1, 0...no pain, 10...worst pain)	VAS during follow-up	12 weeks
Medication use	Pain and rescue medication consumption during treatment and follow-up phase	20 weeks
Heart Rate	Change in heart rate over therapy and follow-up	20 weeks
Heart Rate Variability	Change in heart rate variability over therapy and follow-up	20 weeks
Blood Pressure	Change in blood pressure over therapy and follow-up	20 weeks
Patient motility	Change in daily step count over therapy and follow-up	20 weeks
painDETECT	painDETECT questionnaire over treatment and follow-up	20 weeks
EQ-5D-5L	EQ-5D-5L questionnaire over treatment and follow-up	20 weeks
HADS	Hospital Anxiety and Depression Score (HADS) over treatment and follow-up	20 weeks
Sleep quality	Sleep quality (5-item questionnaire) over treatment and follow-up	20 weeks
Wellbeing	Subjective wellbeing (on a 3-point ordinal scale: good, medium, bad)	20 weeks
Perception Scale	AuriMod CT01 Perception Scale evaluating the quality of stimulation perception in a 10-item questionnaire at EoT	8 weeks
Usability Scale	AuriMod CT01 Usability scoring using the System Usability Scale (10-item scale from 10-50, 10...worst usability, 50...best usability) at EoT	8 weeks
Socioeconomic data	Socioeconomic data change over treatment and follow-up	20 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Outcome 1	Incidence of Adverse Events (AEs) and Device Deficiencies (DDs) observed until EoT	8 weeks
Safety Outcome 2	Incidence of Serious Adverse Events (SAEs) and related AEs observed until end of follow-up	20 weeks

Collaborators and Investigators

• Sponsor: Aurimod GmbH
• Collaborators: La Tour Hospital; Klinikum Klagenfurt am Wörthersee
• Investigators: Principal Investigator: Rudolf Likar, Univ.-Prof. Dr., Abteilung für Anästhesiologie und Intensivmedizin, Klinikum Klagenfurt am Wörthersee, Feschingstrasse 11, 9020 Klagenfurt am Wörthersee, Austria; Principal Investigator: Christophe Perruchoud, PD Dr., Clinique de la Douleur, Hopital de La Tour, Avenue Jacob-Daniel Maillard 3, 1217 Meyrin, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2021
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): October 1, 2022

Study Registration Dates

• First Submitted: January 27, 2021
• First Submitted That Met QC Criteria: February 9, 2021
• First Posted (Actual): February 15, 2021

Study Record Updates

• Last Update Posted (Actual): March 10, 2022
• Last Update Submitted That Met QC Criteria: March 9, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Vagus Nerve Stimulation; Personalization; Therapy Management
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain; Low Back Pain
• Other Study ID Numbers: AT-MF-000000433-CIV-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No